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World J Gastrointest Oncol. Sep 15, 2022; 14(9): 1654-1664
Published online Sep 15, 2022. doi: 10.4251/wjgo.v14.i9.1654
Liquid biopsy to detect resistance mutations against anti-epidermal growth factor receptor therapy in metastatic colorectal cancer
Guillermo Valenzuela, Mauricio Burotto, Katherine Marcelain, Jaime González-Montero
Guillermo Valenzuela, Katherine Marcelain, Jaime González-Montero, Department of Basic and Clinical Oncology, University of Chile, Santiago 8380453, Chile
Guillermo Valenzuela, Department of Internal Medicine, Hospital del Salvador, Santiago 7500922, Chile
Mauricio Burotto, Jaime González-Montero, Department of Oncology, Bradford-Hill Clinical Research Center, Santiago 8420383, Chile
Author contributions: Valenzuela G wrote the manuscript and created the figures and tables; Burotto M, Marcelain K, and González-Montero J performed data collection and literature review and critically revised the manuscript; All authors have approved the final version of the manuscript for publication.
Supported by Agencia Nacional de Investigación y Desarrollo de Chile, Fondo Nacional de Investigación en Salud (FONIS), No. SA20I0059.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jaime González-Montero, MD, PhD, Assistant Professor, Department of Basic and Clinical Oncology, University of Chile, Independencia 1027, Casilla 70058, Santiago 8380453, Chile. jagonzalez@ug.uchile.cl
Received: March 19, 2022
Peer-review started: March 19, 2022
First decision: May 12, 2022
Revised: May 19, 2022
Accepted: August 9, 2022
Article in press: August 9, 2022
Published online: September 15, 2022
Processing time: 173 Days and 15.9 Hours
Abstract

Colorectal cancer (CRC) is a major cause of mortality worldwide, associated with a steadily growing prevalence. Notably, the identification of KRAS, NRAS, and BRAF mutations has markedly improved targeted CRC therapy by affording treatments directed against the epidermal growth factor receptor (EGFR) and other anti-angiogenic therapies. However, the survival benefit conferred by these therapies remains variable and difficult to predict, owing to the high level of molecular heterogeneity among patients with CRC. Although classification into consensus molecular subtypes could optimize response prediction to targeted therapies, the acquisition of resistance mutations to targeted therapy is, in part, responsible for the lack of response in some patients. However, the acquisition of such mutations can induce challenges in clinical practice. The utility of liquid biopsy to detect resistance mutations against anti-EGFR therapy has recently been described. This approach may constitute a new standard in the decision algorithm for targeted CRC therapy.

Keywords: Colorectal neoplasms; Precision medicine; Liquid biopsy; Cetuximab; Panitumumab

Core Tip: Contemporary management of metastatic colorectal cancer patients with wild type KRAS includes the use of anti-epidermal growth factor receptor (EGFR) agents, such as cetuximab or panitumumab, as first-line treatment. However, a significant number of patients receiving this treatment show disease progression. Some of the relapses could be explained by the presence of acquired resistance mutations in KRAS. Liquid biopsy of circulating tumor cells or circulating cell-free DNA is expected to improve the management of patients undergoing anti-EGFR therapy.